The New York Police Department says officers responded to the home in Queens shortly before midnight Saturday.
Two 4-year-olds, a boy and a girl, were pronounced dead at St. John's Episcopal Hospital. Police have identified the boy as Jai'Launi Tinglin and the girl as Ayini Tinglin. They shared the same father.
Their 4-year-old sister is hospitalized in stable condition at St. John's. It wasn't immediately clear whether she was the twin of the boy or the girl who died.
A 55-year-old woman and a 63-year-old man are listed in stable condition at other hospitals.
An investigation into the fire is ongoing.